Major Outcomes in High Risk Hypertensive Patients Randomized to AngiotensinConverting Enzyme Inhibit

1
Major Outcomes in High Risk Hypertensive Patients
Randomized to Angiotensin-Converting Enzyme
Inhibitor or Calcium Channel Blocker vs Diuretic

• The Antihypertensive and Lipid-Lowering Treatment
  to Prevent Heart Attack Trial (ALLHAT)

The ALLHAT Collaborative Research Group Sponsored
by the National Heart, Lung, and Blood Institute
(NHLBI)
www.allhat.org JAMA 20022882981-2997
2
AntihypertensiveTrial Design

• Randomized, double-blind, multi-center clinical
  trial
• Determine whether occurrence of fatal CHD or
  nonfatal MI is lower for high-risk hypertensive
  patients treated with newer agents (CCB, ACEI,
  alpha-blocker) compared with a diuretic
• 42,418 high-risk hypertensive patients 55 years

3
Background

• In addition to their BP lowering potential all
  antihypertensive agents have other important
  mechanisms of action and indications.
• These actions may convey benefits or risks
  independent of BP lowering
• By having a common BP goal for all treatment
  arms, ALLHAT aimed to evaluate the health effects
  of these non-BP actions

4
Secondary Outcomes

• All-cause mortality
• Stroke
• Combined CHD nonfatal MI, CHD death, coronary
  revascularization, hospitalized angina
• Combined CVD (CHD, stroke, coronary
  revascularizations, heart failure treated
  non-hospitalized, hospitalized, fatal, angina
  (treated non-hospitalized, hospitalized),
  peripheral arterial disease (revascularization
  procedure)

5
Secondary Outcomes(Continued)

• HQOL (Health-related quality of life)
• GI Bleeding
• Costs

6
Step 1Treatment Protocol
7
Step UpTreatment Protocol
8
Baseline Characteristics
9
On Step 1 or Equivalent Treatment by
Antihypertensive Treatment Group
10
BP Results by Treatment Group
Compared to chlorthalidone SBP significantly
higher in the amlodipine group (1 mm Hg) and the
lisinopril group (2 mm Hg).
Compared to chlorthalidone DBP significantly
lower in the amlodipine group (1 mm Hg).
11
Blood Pressure Control
2.0
1.8
1.7
1.6
1.4
_at_ 5 years 62 were on gt2 drugs 30 were on 1
drug and controlled
Cushman, et al. J Clin Hypertens 20024393-404
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Biochemical Results
plt.05 compared to chlorthalidone Ann Intern
Med. 1999130461-470
13
ALLHATUSE OF POTASSIUM SUPPLEMENTATION
on potassium suppl.
14
Biochemical Results Fasting Glucose mg/dL
plt.05 compared to chlorthalidone
15
Renal Outcomes
C Chlorthalidone A Amlodipine L Lisinopril
16
Cumulative Event Rates for the Primary Outcome
(Fatal CHD or Nonfatal MI) by ALLHAT Treatment
Group
Chlorthalidone Amlodipine Lisinopril
Number at Risk

Chlorthalidone

15,255

14,477

13,820

13,102

11,362

6,340

2,956

209
Amlodipine

9,048

8,576

8,218

7,843

6,824

3,870

1,878

215
Lisinopril

9,054

8,535

8,123

7,711

6,662

3,832

1,770

195
17
Cumulative Event Rates for Stroke by ALLHAT
Treatment Group
Chlorthalidone Amlodipine Lisinopril
Number at risk

Chlor

15,255

14,515

13,934

13,309

11,570

6,385

3,217

567

Amlo

9,048

8,617

8,271

7,949

6,937

3,845

1,813

506

Lisin

9,054

8,543

8,172

7,784

6,765

3,891

1,828

949


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Stroke Subgroup Comparisons RR (95 CI)
19
Cumulative Event Rates for All-Cause Mortality by
ALLHAT Treatment Group
Chlorthalidone Amlodipine Lisinopril
Number at risk





Chlor

15,255

14,933

14,564

14,077

12,480

7.185

3,523

428

Amlo

9,048

8,847

8,654

8,391

7,442

4,312

2,101

217

Lisin

9,054

8,853

8,612

8,318

7,382

4,304

2,121

144


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Cumulative Event Rates for Combined CVD by ALLHAT
Treatment Group
Chlorthalidone Amlodipine Lisinopril
Number at risk

Chlor

15,255

13,752

12,594

11,517

9,643

5,167

2,362

288

Amlo

9,048

8,118

7,451

6,837

5,724

3,049

1,411

153

Lisin

9,054

7,962

7,259

6,631

5,560

3,011

1,375

139


21
Combined CVD Subgroup Comparisons RR (95 CI)
22
Cumulative Event Rates for Heart Failure by
ALLHAT Treatment Group
Chlorthalidone Amlodipine Lisinopril
Number at risk

Chlor

15,255

14,528

13,898

13,224

11,511

6,369

3,016

384

Amlo

9,048

8,535

8,185

7,801

6,785

3,775

1,780

210

Lisin

9,054

8,496

8,096

7,689

6,698

3,789

1,837

313

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Overall Conclusions
Because of the superiority of thiazide-type
diuretics in preventing one or more major forms
of CVD and their lower cost, they should be the
drugs of choice for first-step antihypertensive
drug therapy.